The specific aims of this research are: (a) to purify and characterize in greater detail the nature of the long-acting thyroid stimulator (LATS) and the substance(s) which inactivate LATS (b) investigate further the roles of humoral and cellular immunity in the genesis of Graves' disease (c) induce in animals a model of Graves' disease, especially Graves' ophthalmopathy (d) study in man genetic determinants of anti-thyroid antibody production and of thyroid disease incidence (e) continue clinical studies which correlate immunologic and pathologic phenomena with the onset, maintenance, or remission of clinical manifestations of Graves' disease. Using membranes prepared from human or bovine orbital muscles, the binding in vitro to them of thyroglobulin (Tg) and thyroglobulin- antithyroglobulin complex (Tg-A)will be studied further. Attempts will be made to detect and measure Tg-A immune complexes in serum. The fate of administered Tg and Tg-A will be studied in rabbits. The binding of processed potent LATS-IgG to purified thyroid cell membranes will be studied. Histocompatibility antigen identification will be determined in patients with Graves' disease, Hashimoto's thyroiditis, and thyroid cancer. Patients with Graves' ophthalmopathy will be treated with supervoltage orbital irradiation.